Schematic representation of human Ca_V2.1 mutations causing episodic ataxia type 2 (EA2). Please note that residue numbering varies between studies due to the existence of multiple CACNA1A splice variants; residue numbers indicated reflect those stated in the original report. Citations to the indicated mutations are listed as follows: E147K—Imbrici et al., 2004; G162V—Maksemous et al. (2016); R192W—Soden et al. (2014); R198Q—Indelicato et al. (2019); Y248C—Zafeiriou et al. (2009); Y248N—Choi et al. (2017); H253Y—van den Maagdenberg et al. (2002); C256R—Mantuano et al. (2004); R279C—Maksemous et al. (2016); C287Y—Jen et al. (2004); G293R—Yue et al. (1997); G297R—Tantsis et al. (2016); D302N—Maksemous et al. (2016); R387G—Maksemous et al. (2016); E388K—Nikaido et al. (2011); L389F—Mantuano et al. (2010); G411W—Maksemous et al. (2016); A454T—Cricchi et al. (2007); R455Q—Isaacs et al. (2017); T501M—Mantuano et al. (2010); G533K—Scoggan et al. (2006); G540R—Rajakulendran et al. (2010a); L621R—Rajakulendran et al. (2010a); G638D—Cuenca-León et al. (2009); I712V—Guerin et al. (2008); M798T—Mantuano et al. (2010); P897R—Mantuano et al. (2010); F1404C—Jen et al. (2001); R1433Q—Pietrobon (2010); G1483R—Mantuano et al. (2004); F1491S—Guida et al. (2001); V1494I—Mantuano et al. (2004); R1662H—Friend et al. (1999); R1665Q—Tonelli et al. (2006); R1680C—Mantuano et al. (2010); H1737L—Spacey et al. (2004); L1749P—Maksemous et al. (2016); R1751W—Bertholon et al. (2009); E1757K—Denier et al. (2001); S1799L—Ohba et al. (2013); C1870R—Mantuano et al. (2010); R2090Q—Melzer et al. (2010); R2136C—Mantuano et al. (2004); P2222L—Sintas et al. (2017). The Ca_V2.1 schematic was modified from Tyagi et al. (2019) with permission of the authors.

Schematic representation of human Ca_V2.1 mutations causing familial hemiplegic migraine type 1 (FHM1). Please note that residue numbering varies between studies due to the existence of multiple CACNA1A splice variants; residue numbers indicated reflect those stated in the original report. Citations to the indicated mutations are listed as follows: R192Q—Ophoff et al. (1996); R195K—Ducros et al. (2001); S218L—Kors et al. (2001); P225H—Stuart et al. (2012); G230V—Yang et al. (2014); F363S—Riant et al. (2010); V581M—Cuenca-León et al. (2008); V581L—Freilinger et al. (2011); R583Q—Battistini et al. (1999); T666M—Ophoff et al. (1996); V714A—Ophoff et al. (1996); D715E—Ducros et al. (2001); E1015K—Grieco et al. (2018); Y1245C—Cuenca-León et al. (2008); K1336E—Ducros et al. (2001); R1347Q—Alonso et al. (2004); C1370Y—Thomsen et al. (2007); Y1385C—Vahedi et al. (2000); V1457L—Carrera et al. (1999); F1506S—Riant et al. (2010); F1506Y—Pelzer et al. (2018); I1512T—Grieco et al. (2018); C1535S—Dichgans et al. (2005); F1609L—Pelzer et al. (2018); R1668W—Ducros et al. (2001); K1670R—Riant et al. (2010); L1682P—Weiss et al. (2007); W1684R—Ducros et al. (2001); V1696I—Ducros et al. (2001); I1710T—Kors et al. (2004); D1725N—Riant et al. (2010); I1811L—Ophoff et al. (1996); A2006T—Wilson (2014); R2157G—Grieco et al. (2018). The Ca_V2.1 schematic was modified from Tyagi et al. (2019) with permission of the authors.

Missense Ca_V2.1 mutations leading to neurodevelopmental disorders. The zebrafish fakir and tb204a mutants are also depicted as yellow circles. Red circles indicate a loss-of-function human mutation. Blue circles indicate a gain-of-function human mutation. Magenta circles indicate a yet-to-be functionally characterized human mutation. Specific references are indicated below. As in Figures 1, 2, please note that residue numbering varies between studies due to: (1) the existence of multiple known CACNA1A splice variants; and (2) species differences between humans and zebrafish. The Ca_V2.1 schematic was modified from Tyagi et al. (2019) with permission of the authors. These mutations are discussed in sections “The Expanding Spectrum OF Ca_V2.1-α_1A Channelopathies” and “Zebrafish as a Model SYSTEM for the Study of Severe Ca_V2.1 Channelopathies.”